Liver pemoline

Methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and pemoline (Cylert) are currently available in the United States. Methylphenidate has been the most widely used and is usually the first choice. Pemoline sometimes impairs liver function and is rarely used today due to the potential for toxicity. 

The greatest concern is that pemoline on rare occasions causes a chemical hepatitis (liver malfunction). For this reason, patients with known liver disease should never take pemoline. Patients should have a baseline laboratory assessment of liver... 

Although side effects of other stimulants respond to dose reduction or change in time of administration, PEM use can be associated with serious, irreversible liver damage. Postmarketing surveillance revealed abnormalities in liver function tests in 44 children receiving PEM acutely or chronically (Berkovitch et ah, 1995). Even more disturbing, 13 children on PEM experienced total liver failure—11 resulting in death or transplant within 4 weeks of failure. This exceeds the rate in the normal population by 4 to 17 times. Pemoline, therefore, is reserved for alternative treatment only if the patient fails to tolerate all three stimulants (MPH, DEX, and AMP) and subsequent trials of an-... 

Berkovitch, M., Pope, E., Phillips, J., and Koren, G. (1995) Pemoline-associated fulminant liver failure testing the evidence for causation. Clini Pharmacol Ther 57 696—698. 

Pemoline has effect of rare serious hepato-toxicity requires monitoring of liver function tests... 

Pemoline (Cylert), (112.5 to 185.5 mg) was assessed in a 3-week open trial in 15 adolescents with CD, ADHD, and SUD (Riggs et ah, 1996). Three of the subjects were receiving other psychotropic medications (clonidine (Catapres) and paroxetine [Paxil]). All subjects had a significant improvement in ADHD symptoms (p <0.002) while 10/13 reported that the pemoline (Cylert) assisted in their substance rehabilitation. No subjects developed a significant elevation in their liver function tests, nor did any subjects test positive for substances of abuse for the duration of the study. No interactions between pemoline (Cylert) and any substances of abuse were reported. 

Pemoline has been associated with 13 cases of hepatic failure since 1975. These cases have principally occurred in children younger than 10 years of age who were taking at least one other drug in addition to pemoline. Although rare, these cases have raised considerable debate as to whether pemoline has a role in the treatment of ADHD. If pemoline is used, liver function tests are recommended at baseline and then every 2 weeks. The efficacy of pemoline is based on a double-blind study involving both a placebo and active (methylphenidate) comparison treatment arm ( 73). Nevertheless, the magnitude of its effect is generally not as... 

As an aside, in March of 2005, Abbott Laboratories, the maker of Cylert , decided to take its drug off the U.S. market because of increasing concerns about it causing liver problems. Cylert had been available in the United States for 30 years for the treatment of ADHD and narcolepsy. However, the generic form of Cylert (pemoline) is still available. 

The most commonly used agents to enhance attention in attention deficit disorder are the stimulants methylphenidate and ( -amphetamine. Other effective stimulants are not as widely used, pemoline because of liver toxicity and methamphetamine because of its greater abuse potential. Methylphenidate and ( -amphetamine act predominantly by releasing dopamine from presynaptic dopamine terminals (Figs. 12— 2 and 12—3). These agents not only block the dopamine transporter but may actually... 

Pemoline, an oxizolidine compound, acts similarly to methylphenidate—through catecholamine uptake inhibition in the CNS (27) with minimal sympathomimetic effects (57). Although pemoline is not the first-line stimulant for the treatment of ADHD, it has been successfully used for the treatment of this disorder in both children and adults (28,30). Pemoline has also been used for the treatment of daytime sleepiness associated with narcolepsy (31), and although it is somewhat effective for this purpose (33), it is not a first-line choice owing to its potentially lethal liver toxicity. 

Pemoline has a peak effect of 4 hr with an 8-hr duration of action and a half-life of 12 hr in adults. It is metabolized by the liver, with approximately 50% excreted unchanged in the urine (57). Although drug levels peak fairly quickly, clinical improvement may not be seen until after 3 1 weeks of treatment (36). 

As with methylphenidate, the adverse effects associated with pemoline are generally mild. The most common effects are insomnia, decreased appetite, stomachache, headache, and jitteriness (28). Periodic monitoring of liver enzymes is necessary because of the potential for hepatic toxic effects. 

At present, there is no way to predict who is likely to develop liver tailure however, only patients without liver disease and with normal baseline liver tunction tests should initiate pemoline therapy... 

Pemoline should be discontinued if serum ALT (SGPT) is increased to a clinically significant level, if any increase >2 times the upper limit of normal occurs, or if clinical signs and symptoms suggest liver failure... 

If pemoline therapy is discontinued and then restarted, the liver testing should be done prior to reinitiating treatment and then every 2 weeks... 

Thus, liver function monitoring is a necessary component of pemoline therapy... 

During the past two decades there have been many reports of liver failure resulting in death or transplantation in patients being treated for ADHD with pemoline. However, a descriptive meta-analysis of the existing scientific literature and drug reporting databases showed that current assumptions of the risk of acute hepatic failure posed by pemoline alone are overestimates. 

A 7-year-old boy with Duchenne muscular dystrophy and attention deficit hyperactivity disorder (ADHD) developed acute hepatic failure, with features of autoimmune hepatitis (2). The only medications he had taken were pemoline (56 mg/day) and cjrproheptadine (2 mg/day). Pemoline was withdrawn after 8 months as the presumed cause of his raised transaminases. Two weeks later he developed an altered mental state, jaundice, and encephalopathy. The histological features of the liver and his autoimmune antibody panel were consistent with autoimmune hepatitis. He was treated with corticosteroids and azathioprine and recovered. 

A 9-year-old boy with ADHD taking pemoline developed signs and symptoms of liver failure requiring liver transplantation (3). 

The evidence linking pemoline to life-threatening liver failure prompted the Food and Drugs Administration to require the manufacturer to add a black box warning to the package insert, whereas in the UK the Committee on Safety of Medicines withdrew marketing approval for pemohne, citing safety and a lack of adequate evidence of efficacy as the reason (4). 

Adcock KG, MacElroy DE, Wolford ET, Farrington EA. Pemoline therapy resulting in liver transplantation. Ann Pharmacother 1998 32(4) 422-5. 

Medications play an important part in the treatment of ADD. Stimulants are the mainstay of the treatment of ADD methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and pemoline (Cylert). These differ in their half-lives, with Ritalin having the shortest and Cylert the longest. A warning has recently been issued about Cylert because of reports of sometimes fatal liver toxicity. Thus, it is recommended that it be used only if methylphenidate and dextroamphetamine are ineffective. There is individual variability in resporise, so that a person who does not respond to one may respond well to another. Other medications can also be effective in the treatment of ADD and may be useful, especially in residual ADD, where substance abuse may be an issue. These include tricyclic antidepressants (especially desipramine and imi-pramine) SSRIs, bupropion, venlafaxine, and clonidine. There are reports of antipsy-chotics and lithium being helpful in selected cases, as well. 

A Pemoline (Cylert) Mild CNS stimulant. Actions similar to d-amphetamine. Attention deficit disorder. Insomnia, anorexia, liver dysfunction (usually reversible). 

Abbiati C, Vecchi M, Rossi G, Donata MF, de Franchis R (2002) Inappropriate pemoline therapy leading to acute liver failure and liver transplantation. Dig Liver Dis 34 447 51 Ackerman Z, Levy M (1987) Hypersensitivity reactions to drugs in acquired immunodeficiency syndrome. Postgrad Med J 63 55-56... 

B. Pharmacokinetics. All these drugs are well absorbed orally and have large volumes of distribution (Vd = 3-33 L/kg, except pemoline, with Vd = 0.2-0.6 L/kg), and they are generally extensively metabolized by the liver. Excretion of most amphetamines is highly dependent on urine pH, with amphetamines being more rapidly eliminated in an acidic urine (see also Table 11-59, p 381). 

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